7. Project Summary/Abstract The majority of human monkeypox (MPX) infections occur each year in the Democratic Republic of Congo (DRC), notably among rural populations that are highly dependent on bushmeat as a source of protein local resources to sustain villages. In the present project proposal, we propose a range of activities to better understand the epidemiology and ecology of MPX, clinical interventions to prevent human MPX infections, clinical follow-up to better understand the parameters of human MPX virus infections, improvement of laboratory diagnostic surveillance and point-of-care testing, and community and healthcare worker education. The goal of this project is to determine effective epidemiological and clinical interventions that minimize human morbidity and mortality by a) diminishing the risk of infection and b) identifying opportunities to utilize medical countermeasures for treatment. Maintenance of the existing enhancements to laboratory-based MPX surveillance in Tshuapa Province will continue, as detection and confirmation of disease has direct impacts on the current and proposed studies. We will continue to implement ecological and epidemiological investigations of MPX cases and at-risk communities to better understand specific behaviors or environments that place individuals at higher risk in order to develop more targeted, evidence-based prevention strategies. Accurate geographic data will be collected in Tshuapa to better inform ecological, epidemiological, and health systems public health analyses. We will continue to implement and evaluate educational messaging for communities and healthcare workers to prevent MPX infections and better inform research studies. The project will continue to implement an existing research protocol to assess the effectiveness of a third-generation smallpox vaccine to prevent MPX infection in a high-risk group with frequent exposures. Data from this study will be reviewed to assess the potential for post-exposure vaccination to protect close contacts of MPX patients. The project will also review the limited evidence on MPX disease presentation and supportive care regimens to develop and implement a protocol to follow MPX patients in order to evaluate disease presentation with respect to clinical care, with the goal of improving patient outcomes. We will assess approaches to improve the timeliness of MPX diagnosis in DRC by implementation of MPX and Orthopoxvirus testing using existing capacity at regional laboratories in the country. Biosafety and biosecurity practices will be evaluated at select laboratories located in regions with MPX cases and independent validation of test results will be performed at the national laboratory. We will also validate the use of a point-of- care diagnostic test in a setting where patient treatment occurs, evaluating the user operability and acceptance of a lateral flow diagnostic assay to diagnose MPX cases.